Administration of para-chloroamphetamine to animals resulted in long-term destruction of serotonergic neurons in the brain. Evidence suggests that the neurotoxicity is due to an unidentified reactive metabolite which may be formed in the brain. The neurotoxicity of the enantiomer of para-chloroamphetamine is different. In addition, the enantiomers of related 1-phenyl-2-aminopropanes are metabolized differently. The premise of this proposal is that there may be a relationship between the stereochemical nature of para-chloroamphetamine neurotoxicity and its metabolism. A study of the sterochemical nature of para-chloroamphetamine metabolism in two well defined and relevant systems is proposed. Liver microsomes, which support oxidative covalently binds to macromolecules. Brain microsomes also support oxidative metabolism, and formation of the toxic intermediate in the brain has been suggessted. These facts, and the sterochemical nature of para-chloroamphetamine neurotoxicity, lead to this proposal to study he dissappearance of the enantiomers of para-chloroamphetamine in fortified rat liver and brain microsomes. This will be accomplished with a new gas chromatographic assay which allows determination of the enantiomers after reaction with a chiral derivatizing agent to yield disastereomers. The enantiomers may also be determined after administration of the racemate. Techniques involved in these studies are familiar to the investigator, and results will contribute to an understanding of the role of stereochemistry and metabolism in the neurotoxicity of para-chloroamphetamine.